Abstract
Rv3852 is a unique nucleoid-associated protein (NAP) found exclusively in Mycobacterium tuberculosis (Mtb) and closely related species. Although annotated as H-NS, we showed previously that it is very different from H-NS in its properties and is distinct from other NAPs, anchoring to cell membrane by virtue of possessing a C-terminal transmembrane helix. Here, we investigated the role of Rv3852 in Mtb in organizing architecture or synthesis machinery of cell wall by protein–protein interaction approach. We demonstrated a direct physical interaction of Rv3852 with Wag31, an important cell shape and cell wall integrity determinant essential in Mtb. Wag31 localizes to the cell poles and possibly acts as a scaffold for cell wall synthesis proteins, resulting in polar cell growth in Mtb. Ectopic expression of Rv3852 in M. smegmatis resulted in its interaction with Wag31 orthologue DivIVAMsm. Binding of the NAP to Wag31 appears to be necessary for fine-tuning Wag31 localization to the cell poles, enabling complex cell wall synthesis in Mtb. In Rv3852 knockout background, Wag31 is mislocalized resulting in disturbed nascent peptidoglycan synthesis, suggesting that the NAP acts as a driver for localization of Wag31 to the cell poles. While this novel association between these two proteins presents one of the mechanisms to structure the elaborate multi-layered cell envelope of Mtb, it also exemplifies a new function for a NAP in mycobacteria.
Highlights
Lack of a nuclear membrane presents bacteria with an exigent task of compacting their genome in a small cytoplasmic volume
Genome maintenance and DNA transactions are orchestrated by only a few nucleoid-associated protein (NAP) in Mycobacterium tuberculosis (Mtb), as opposed to Escherichia coli (E. coli) and other wellstudied bacteria that possess more than a dozen NAPs
The unusual membrane localization of Rv3852 suggested an unusual function for the NAP in biology of Mtb
Summary
Lack of a nuclear membrane presents bacteria with an exigent task of compacting their genome in a small cytoplasmic volume. The highly basic proteins, known as the nucleoidassociated proteins (NAPs), are associated with the nucleoid, enabling it to segregate, replicate, and transcribe in a manner appropriate to the needs of the bacterium [1]. NAPs play a crucial role in maintaining the spatio-temporal organization of the nucleoid and influence gene expression through topological changes such as coating, bending, wrapping, and bridging DNA [2,3]. Genome maintenance and DNA transactions are orchestrated by only a few NAPs in Mycobacterium tuberculosis (Mtb), as opposed to Escherichia coli (E. coli) and other wellstudied bacteria that possess more than a dozen NAPs. Different mycobacterial NAPs can act as mediators for different forms of intracellular stress.
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